2. Academic Validation
  3. Direct sensing of dietary ω-6 linoleic acid through FABP5-mTORC1 signaling

Direct sensing of dietary ω-6 linoleic acid through FABP5-mTORC1 signaling

  • Science. 2025 Mar 14;387(6739):eadm9805. doi: 10.1126/science.adm9805.
Nikos Koundouros 1 2,  Michal J Nagiec 1 2,  Nayah Bullen 1,  Evan K Noch 1 3,  Guillermo Burgos-Barragan 1 2,  Zhongchi Li 1 2,  Long He 1 2,  Sungyun Cho 1 2,  Bobak Parang 1 2 4,  Dominique Leone 5,  Eleni Andreopoulou 6,  John Blenis 1 2 7
Affiliations

Affiliations

  • 1 Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
  • 2 Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA.
  • 3 Department of Neurology, Division of Neuro-oncology, Weill Cornell Medicine, New York, NY, USA.
  • 4 Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
  • 5 Cancer Clinical Trials Office - Breast, Weill Cornell Medicine, New York, NY, USA.
  • 6 Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY, USA.
  • 7 Department of Biochemistry, Weill Cornell Medicine, New York, NY, USA.
PMID: 40080571 DOI: 10.1126/science.adm9805
Abstract

Diet influences macronutrient availability to cells, and although mechanisms of sensing dietary glucose and Amino acids are well characterized, less is known about sensing lipids. We defined a nutrient signaling mechanism involving fatty acid-binding protein 5 (FABP5) and mechanistic target of rapamycin complex 1 (mTORC1) that is activated by the essential polyunsaturated fatty acid (PUFA) ω-6 linoleic acid (LA). FABP5 directly bound to the regulatory-associated protein of mTOR (Raptor) to enhance formation of functional mTORC1 and substrate binding, ultimately converging on increased mTOR signaling and proliferation. The amounts of FABP5 protein were increased in tumors and serum from triple-negative compared with those from receptor-positive breast Cancer patients, which highlights its potential role as a biomarker that mediates cellular responses to ω-6 LA intake in this disease subtype.

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